The concept of the action of radiation as a stimuli is innovative. The aim the present study was to clarify the genetic control mechanisms of the radiation response and to establish a new biological basis of the effects of radiations. In response to small doses of radiations, mammalian cells become radioresistant (adaptive response) as well as stimulated to grow. The adaptive response were found to be mediated by PKC and p38 MAP kinase signalling pathways and continued for long time. While direct relationship was not known, p53 proteins were suggested to be downstream effector of the adaptive response (Sasaki). p53 proteins coprecipitate with heat-shock proteins such as HSP72 (Ohnishi), suggesting regulation of p53 by HSP.p53 proteins are also accumulated in response to microgravity indicating a key role of p53 in general stress response (Ohnishi). In p53 knock-out mouse cells, adaptive response was not induced (Sasaki) and UV-induced mutation showed different spectra as compared with those in wild-type cells (Ishizaki). These findings suggest that p53 regulates DNA replication and thence types and frequencies of mutations. In vitro assay system was established for the repair kinetics of formyluracil, most important oxidative damage to DNA (Yonei). In Drosophila, DNA damage-inducible mutagenesis was confirmed by the mutation of minisatellite loci in female genome fertilized by irradiated sperm, suggesting DNA damage-inducible genetic instability (Niwa). We were not able to clone a gene (ATM) responsible for ataxia telangiectasia, radiosensitive human disease. However, new mutations of ATM gene were found in Japanese patients (Ejima).